In silico analyses of heat shock protein 60 and calreticulin to designing a novel vaccine shifting immune response toward T helper 2 in atherosclerosis

Karkhah, Ahmad; Saadi, Mahdiye; Nouri, Hamid Reza

doi:10.1016/j.compbiolchem.2017.01.011

Cited by 28 publications

(10 citation statements)

References 41 publications

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“…Recently, developments in synthetic genes technology can be resolved codon usage bias and desired genes can be produced cost-effectively [8]. Codons are rarely used in E. coli such as AGG/AGA (arginine), AUA (isoleucine), CGG (arginine), CCC (proline), CUA (leucine) and GGA (glycine) which were avoided in the synthetic gene [37]. The possibility of high protein expression is correlated to the value of the Codon Adaptation Index [18].…”

Section: Discussionmentioning

confidence: 99%

Applying<i> In Silico</i> Approaches for Designing a Chimeric InaV/N-DFPase Protein and Evaluating its Binding with Diisopropyl-Fluorophosphate

Allahyari

Karami

Tebyanian

et al. 2019

ILNS

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The N-terminal domain of the ice-nucleation protein InaV (InaV-N) of Pseudomonas syringae was applied to display the DFPase on the cell surface. In silico techniques were used to generate a model in order to examine the possibility of DFPase exhibition on the cell surface. The secondary and tertiary structures of a chimeric protein were determined and then, the predicted model was subjected to several repeated cycles of stereochemical evaluation and energy minimization. The homology-modeled structure of the InaV/N-DFPase protein was docked to DFP. The optimized inaV/N-dfpase gene was translated to 519 amino acids. The minimum free energy of the best-predicted secondary structures was formed by RNA molecules (-215.45 kcal/mol). SOPMA analysis results showed that the main helix peak corresponded to the anchor fragment. Validation of the 3D model indicated that 86.1% of amino acid residues were incorporated into the favored regions. The moldock score was 360.22 for DFP. Results of this study indicated that according to in silico analysis, all of these findings were effective in targeting DFPase.

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Section: Discussionmentioning

confidence: 99%

Applying<i> In Silico</i> Approaches for Designing a Chimeric InaV/N-DFPase Protein and Evaluating its Binding with Diisopropyl-Fluorophosphate

Allahyari

Karami

Tebyanian

et al. 2019

ILNS

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“…The IFN-epitope server was used with motif scan and SVM approaches to produce overlapping HTL sequence peptides against the query protein [ 45 ]. The IL-4Pred server enables to plan, detect, and map peptides that really can induce IL-4 with a threshold value of 0.2, which is important for subunit vaccines [ 46 ]. IL-10Pred was also used to predict the inducing properties at the threshold value of −0.3 [ 47 ].…”

Section: Methodsmentioning

confidence: 99%

Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis

et al. 2021

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Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium are the main pathogenic species that infect humans. In this research, core proteomics was combined with a subtractive proteomics pipeline to identify suitable antigenic proteins for the construction of a multi-epitope vaccine (MEV) against human-infecting Schistosoma species. The pipeline revealed two antigenic proteins—calcium binding and mycosubtilin synthase subunit C—as promising vaccine targets. T and B cell epitopes from the targeted proteins were predicted using multiple bioinformatics and immunoinformatics databases. Seven cytotoxic T cell lymphocytes (CTL), three helper T cell lymphocytes (HTL), and four linear B cell lymphocytes (LBL) epitopes were fused with a suitable adjuvant and linkers to design a 217 amino-acid-long MEV. The vaccine was coupled with a TLR-4 agonist (RS-09; Sequence: APPHALS) adjuvant to enhance the immune responses. The designed MEV was stable, highly antigenic, and non-allergenic to human use. Molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MMGBSA) analysis were performed to study the binding affinity and molecular interactions of the MEV with human immune receptors (TLR2 and TLR4) and MHC molecules (MHC I and MHC II). The MEV expression capability was tested in an Escherichia coli (strain-K12) plasmid vector pET-28a(+). Findings of these computer assays proved the MEV as highly promising in establishing protective immunity against the pathogens; nevertheless, additional validation by in vivo and in vitro experiments is required to discuss its real immune-protective efficacy.

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“…Oral immunization using peptides from HSP60 together with some from other atherosclerosis-related antigens such as oxLDL and ApoB-100 have also been tested demonstrating effective induction of tolerance featuring the cellular and molecular hallmarks aforementioned; moreover multi-antigenic vaccines using more than two antigenic sources are yet another take on tolerization that is being explored in the search for higher specificity responses. 197,198 In silico modeling is also helpful in predicting the immunogenic and tolerogenic potential of selected antigens for vaccine development and optimization, 199 which makes it a highly valuable tool for future therapeutics of this nature. Note: Experimental evidence on the cellular and molecular changes observed after immunization with HSP60, selected peptides or in association with other antigenic sequences through different administration routes.…”

Section: Tolerization Strategiesmentioning

confidence: 99%

Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story

Krishnan-Sivadoss

Mijares-Rojas

Villarreal-Leal

et al. 2020

Medicinal Research Reviews

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Cardiovascular diseases (CVDs) are the result of complex pathophysiological processes in the tissues comprising the heart and blood vessels. Inflammation is the main culprit for the development of cardiovascular dysfunction, and it may be traced to cellular stress events including apoptosis, oxidative and shear stress, and cellular and humoral immune responses, all of which impair the system's structure and function. An intracellular chaperone, heat shock protein 60 (HSP60) is an intriguing example of a protein that may both be an ally and a foe for cardiovascular homeostasis; on one hand providing protection against cellular injury, and on the other triggering damaging responses through innate and adaptive immunity. In this review we will discuss the functions of HSP60 and its effects on cells and the immune system regulation, only to later address its implications in the development and progression of CVD. Lastly, we summarize the outcome of various studies targeting HSP60 as a potential therapeutic strategy for cardiovascular and other diseases.

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In silico analyses of heat shock protein 60 and calreticulin to designing a novel vaccine shifting immune response toward T helper 2 in atherosclerosis

Cited by 28 publications

References 41 publications

Applying<i> In Silico</i> Approaches for Designing a Chimeric InaV/N-DFPase Protein and Evaluating its Binding with Diisopropyl-Fluorophosphate

Applying<i> In Silico</i> Approaches for Designing a Chimeric InaV/N-DFPase Protein and Evaluating its Binding with Diisopropyl-Fluorophosphate

Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis

Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story

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